Malaria transmission can change rapidly and vary dramatically over small spatial scales. The result is that current maps of malaria epidemiology do not reflect recent changes and have poor predictive capacity at the level of individual communities. Current measures of community exposure to P. falciparum - principally the entomological inoculation rate and parasite rate - have several limitations. Assays of antimalarial antibodies, which can be performed using dried blood spots collected in the field, have recently been shown to provide robust estimates of a community's average exposure to parasites over the prior years. Such assays offer the promise of obtaining frequent, high coverage data on exposure at low cost. However, these assays need to be further refined to reflect dynamic changes in exposure that may occur with implementation of control efforts and to reflect heterogeneity in exposure over small spatial scales. In addition, changes in a population's exposure and therefore immune protection alter the relationship between exposure and disease in a complicated fashion. Assays designed to assess immunologic protection directly would help predict the impact of changing transmission on the burden of disease. In response to the need for better tools to measure exposure and the relationship between exposure and disease, the specific aims of research project 3 are: 1) to characterize the individual-level relationships between P. falciparum exposure, the immune response, and protection from infection and disease in Ugandan cohorts, 2) to develop and validate mmunologic assays for estimating the population-level dynamics of exposure to P. falciparum in surveillance studies performed throughout Uganda, and 3) to develop and validate immunologic assays for estimating the population-level dynamics of disease in response to changing P. falciparum exposure in surveillance studies performed throughout Uganda. Using data and specimens from existing cohorts, laboratory and statistical methods will be optimized to provide immunologic assessments of prior exposure and protection from infection and disease. Immunologic assays will then be translated to the population level and prospectively validated using surveillance data and filter paper blood samples collected at multiples sites in Uganda.